Maternal tobacco consumption is well known to cause fetal growth retardation and neurobehavioral disturbances in the offspring. Yet, due to the addictiveness of nicotine in tobacco 20% of U.S. women of child bearing age are currently cigarette smokers, adding more than 40 billion dollars to the rising health care costs. Unlike in adults, exposure to nicotine even at low doses alters the transmitter synthesis and uptake profiles in the developing sympathetic neurons. [While studies show that acute exposure to nicotine retracts neurites in parasympathetic neurons, effects of prolonged exposure to nicotine on survival and neurite growth in sympathetic neurons are unknown]. Our preliminary results show that nicotine exposure retards neurite growth while protecting neurons from cell death in response to the challenge of trophic factor withdraw! in neonatal sympathetic neurons of rat. Based on these results, this proposal will test the hypothesis that chronic exposure to nicotine retards neurite growth in the neonatal developing sympathetic neurons due to altered influx of calcium via the calcium permeable nicotinic receptors. To achieve this, two studies are proposed in specific aims: (1) determine the dose and time dependent effects of nicotine exposure on neuron survival and neurite growth in the neonatal sympathetic neurons, and (2) investigate if chronic nicotine exposure alters intraneuronal calcium levels in these neurons, mediated by specific subtype(s) of nicotinic receptors. Primary cultures of SCO neurons of new born rat pups will be used for these studies since the controlled in vitro environment allows for investigating the direct effect of nicotine. Morphometry, calcium imaging, immunocytochemistry, immuno blotting and receptor binding assays will be used to achieve these aims. Results from these experiments will begin to reveal the mechanism of nicotine's action on survival and neurite growth in sympathetic neurons and form the basis for future studies to investigate the link between nicotine and neurogenic mechanisms underlying deficits in sympathetic regulation in children exposed to nicotine during development. [Understanding the mechanism of action of nicotine on the developing sympathetic neurons will lead to finding possible means to treat children of cigarette smokers. These studies will also provide crucial research experience to undergraduate students to stimulate their interest in biomedical research while educating them about the harmful effects of smoking]. [unreadable] [unreadable]